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Simvastatin attenuates release of neutrophilic and remodeling factors from primary bronchial epithelial cells derived from stable lung transplant recipients

Lookup NU author(s): Emeritus Professor Mike Sir Michael Rawlins, Dr Ian Forrest, Emeritus Professor Paul Corris, Therese Small, Debra Jones, Professor Andrew Fisher, Emeritus Professor Tim Cawston, Professor Christopher Ward, Dr James Lordan

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Abstract

Obliterative bronchiolitis (OB), the major cause of chronic lung allograft dysfunction, is characterized by airway neutrophilia, inflammation, and remodeling, with progressive fibroproliferation and obliteration of small airways that ultimately leads to patient death. Statins have potential anti-inflammatory effects and have been demonstrated to confer a survival advantage in lung transplant patients. We postulated that the beneficial effects of simvastatin in lung transplantation are in part due to inhibition of the epithelial production of key mediators of neutrophil chemotaxis, inflammation, and airway remodeling. Our objective was to assess the effect of simvastatin on a unique population of primary bronchial epithelial cells (PBECs) derived from stable lung allografts, with specific reference to airway neutrophilia and remodeling. PBEC cultures were stimulated with IL-17 or transforming growth factor (TGF)-β, with and without simvastatin. Supernatant levels of factors critical to driving airway neutrophilia and remodeling were measured. IL-17 upregulated IL-8, IL-6, granulocyte colonystimulating factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and VEGF, whereas TGF-β increased IL-6, GM-CSF, matrix metalloproteinase (MMP)-2, and MMP-9. Simvastatin attenuated effects of both IL-17 and TGF-β. We have demonstrated the ability of simvastatin to attenuate release of airway neutrophilic and remodeling mediators and to inhibit their upregulation by TGF-β and IL-17. These data illustrate the potential of simvastatin to alleviate neutrophilic airway inflammation and remodeling in the transplanted lung and may have additional relevance to other neutrophilic airway conditions, such as chronic obstructive pulmonary disease. Copyright © 2008 the American Physiological Society.


Publication metadata

Author(s): Murphy DM, Forrest IA, Corris PA, Johnson GE, Small T, Jones D, Fisher AJ, Egan JJ, Cawston TE, Ward C, Lordan JL

Publication type: Article

Publication status: Published

Journal: American Journal of Physiology: Lung Cellular and Molecular Physiology

Year: 2008

Volume: 294

Issue: 3

Pages: L592-L599

ISSN (print): 1040-0605

ISSN (electronic): 1522-1504

Publisher: American Physiological Society

URL: http://dx.doi.org/10.1152/ajplung.00386.2007

DOI: 10.1152/ajplung.00386.2007

PubMed id: 18203812


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